Dry powder inhaler

ABSTRACT

The present invention relates to an inhaler which is appropriate for delivery of medicament in dry powder form used in respiratory diseases, particularly in asthma and chronic obstructive pulmonary disease (COPD). In addition, the present invention relates to an inhaler which includes a blister package appropriate for carrying the medicament in dry powder form and used to realize an effective inhalation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of U.S. Application No. 13/451,838, filedApr. 20, 2012, which is a continuation-in-part of PCT Application No.PCT/TR2010/000210, filed Oct. 20, 2010, and PCT Application Nos.PCT/TR2011/000085, PCT/TR2011/000086, PCT/TR2011/000087,PCT/TR2011/000088, PCT/TR2011/000089, PCT/TR2011/000090,PCT/TR2011/000091, PCT/TR2011/000093, PCT/TR2011/000094, andPCT/TR2011/000095, filed Apr. 13, 2011, each of which is incorporatedherein by reference in its entirety. U.S. application Ser. No.13/451,838 also claims priority to Turkish Patent ApplicationsTR2009/07917, filed Oct. 20, 2009, TR2010/02877, filed Apr. 13, 2010,TR2010/03091, filed Apr. 20, 2010, TR2010/03238, filed Apr. 26, 2010,TR2010/04307, TR2010/04308, TR2010/04310, TR2010/04312, TR2010/04313,and TR2010/04317, filed May 28, 2010.

BACKGROUND OF THE INVENTION

It is rather common to use inhalers for delivering medicaments utilizedin the treatment and prophylaxis of respiratory diseases. Inhalationtreatment is the most commonly preferred treatment method in thesediseases as the inhalers provide ease of use; the medicaments haverapider onset of time resulting from local administration and they havefewer side effects. Various inhalers have been designed in order toprovide effective and sufficient delivery of the medicaments used in thetreatment of respiratory diseases, particularly in asthma and chronicobstructive pulmonary disease. These inhalers vary according to theiroperating mechanisms and the physical form of the medicament to bedelivered.

In the inhalers used to deliver the medicaments in dry powder form, themedicament is carried in reservoirs, capsules or blisters packages. Itis highly significant to deliver each dose to the patient with exactaccuracy and preciseness since the required medicament dose in theinhalation is very low.

In general, one blister pocket containing medicament in dry powder formis opened in response to each actuation of the device in inhalerscomprising blister packages. One blister pocket containing one dose ofdry powder medicament is usually opened by peeling the blister packageindexed upon the actuation of the device or piercing the blister pocketby the piercing means in the inhaler. The inhalers comprising peelableblister packs enable the sufficient amount of the dry powder medicamentcontained in the opened blister to be easily inhaled as the airflowenters the opened blister pocket more easily in the inhalers comprisingpeelable blister packs than the inhalers comprising pierceable blisterpacks. Therefore, the blister package should be indexed enough to enablethe blister pocket to be opened completely so as to realize an effectiveinhalation in response to each actuation of the inhaler. However, it isquite difficult to enable the blister package to be indexed properly tothe same extent in each actuation of the device so as to realize a safeinhalation in the inhaler comprising peelable blister packages. In thecase that the blister package that is indexed upon the actuation of thedevice is indexed less than the required extent, the blister pocket maynot be opened completely while more than one blister pocket may beopened in the case that the blister package is indexed more than therequired extent. The fact that one blister pocket cannot be openedcompletely and an effective inhalation cannot be realized as thesufficient amount of the active agent comprised in the dry powdermedicament cannot be delivered to the patient or more than the requiredamount of the active agent is delivered to the patient as one blisterpockets are opened lead to dangerous consequences. Therefore, controlleddosing of the medicament in dry powder form cannot be achieved when theblister package is not indexed properly to the same extent in responseto each actuation of the inhaler.

The inhalation device marketed under the trade mark Diskus® byGlaxoSmithKline is one of the most well-known inhalers on the market.This device operates with a slide mechanism and a blister strip packagein which the dry powder medicament is carried. However, this deviceneeds to be improved in terms of specifications to enable the blisterpackage to be properly indexed to the same extent in response to eachactuation of the device.

The inventor has surprisingly found that the force of attraction imposedby the winding wheel on the lid sheet is balanced, and thus the blisterpackage is properly indexed to the same extent in response to eachactuation of the device in the case that each of the preferablypolyoxymethylene resilient wings of the winding wheel, on which the lidsheet of the blister package peeled upon the actuation of the inhaler iscoiled, is composed of three parts in the inhaler comprising peelableblister package.

To this respect, the present invention relates to an inhaler comprisingpeelable blister package appropriate for delivering dry powdermedicament which enables the blister package to be indexed properly tothe same extent in response to each actuation of the inhaler.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a is a perspective view of the inhaler according to the presentinvention.

FIG. 1 b is another perspective view of the inhaler according to thepresent invention.

FIGS. 1 c and 1 d are views of the A-A and B-B cross sections of theinhaler of the present invention, respectively.

FIG. 2 a is an exploded view of the inhaler according to the invention.

FIG. 2 b is a vertical cross-sectional view of the inhaler according tothe present invention.

FIG. 2 c is a front view of the inhaler according to the presentinvention.

FIG. 2 d is a lateral view of the inhaler according to the presentinvention.

FIG. 3 is a perspective view of the blister pack for use with theinhaler according to the invention.

FIGS. 4 a and 4 b are perspective views of the housing of the inhaleraccording to the invention.

FIG. 4 c is another perspective view of the housing of the inhaleraccording to the invention.

FIG. 4 d is another perspective view of the housing of the inhaler ofthe invention.

FIGS. 4 e and 4 f are cross-sectional views of the manifold part of theinhaler pertaining to the invention which is shown as X in FIG. 4 c.

FIGS. 4 g and 4 h are perspective plan and bottom views of the housingof the inhaler according to the invention, respectively.

FIGS. 4 i and 4 j are perspective views of the housing and the gearmechanism of the inhaler of the invention.

FIGS. 5 a and 5 b are perspective views of upper and lower housingmembers of the inhaler according to the invention, respectively.

FIG. 5 c is another perspective view of the upper housing member of theinhaler of the invention.

FIG. 5 d is another perspective view of the lower housing member of theinhaler of the invention.

FIGS. 5 e and 5 f are perspective views of the inner and outer sides ofthe upper housing member of the inhaler according to the invention,respectively.

FIGS. 5 g and 5 h are perspective views of the inner and outer sides ofthe lower housing member of the inhaler according to the invention,respectively.

FIG. 5 i is a cross-sectional view of the connection of the stabilizingresilient cover with the lower housing member in the inhaler pertainingto the invention.

FIG. 6 a is a view of the mouthpiece cover exploded from the inhaler.

FIG. 6 b is another perspective view of the mouthpiece cover of theinhaler of the invention.

FIGS. 6 c and 6 d are perspective views of the inner and outer sides ofthe mouthpiece cover of the inhaler according to the invention,respectively.

FIGS. 6 e is a perspective view of the connection between the mouthpiececover, the drive gear, and the protective covers of the inhaler of theinvention.

FIG. 6 f is a perspective of the connection between the mouthpiece coverand the protective covers of the inhaler of the present invention.

FIG. 6 g is a perspective view of the connection between the mouthpiececover, the drive gear, the lower housing member, and the protectivecover of the inhaler of the present invention.

FIG. 6 h is an exploded view of the communication between the mouthpiececover, the drive gear and the stabilizing resilient covers in theinhaler according to the invention.

FIG. 6 i is a cross-sectional view of the communication between themouthpiece cover, the drive gear and the stabilizing resilient covers inthe inhaler according to the invention.

FIG. 6 j is a cross-sectional view of the communication between themouthpiece cover, the drive gear and the stabilizing resilient covers inthe inhaler according to the invention.

FIGS. 7 a and 7 b are cross-sectional views of the engagement of thegears composing the gear mechanism with each other in the inhaleraccording to the present invention.

FIG. 7 c is a cross-sectional view of the engagement of the gearscomposing the gear mechanism in the inhaler of the present invention.

FIG. 7 d is another cross-sectional view of the engagement of the gearscomposing the gear mechanism in the inhaler of the present invention.

FIGS. 7 e and 7 f are perspective views of the drive gear of the inhaleraccording to the invention.

FIG. 7 g is a perspective view of the drive gear of the inhaler of theinvention.

FIG. 7 h is an exploded view of the communication between the drive gearand the side covers in the inhaler according to the invention.

FIG. 8 is a cross-sectional view of the blister package delaminating incourse of operation of the inhaler according to the present invention.

FIG. 9 is a perspective view of the counter gear used in the inhaleraccording to the present invention.

FIGS. 10 a and 10 b are perspective views of the stopper consisting ofthe pawl, the pressing button, and the supporting member used in theinhaler of the present invention.

FIG. 11 is a perspective view of the connection between the indexingwheel and another stopper used in the inhaler of the invention.

FIG. 12 is a perspective view of the winding wheel pertaining to thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

The inhaler pertaining to the present invention is an easy-grip, manualdevice which is suitable to be used for the delivery of the medicamentin dry powder form.

The housing of the device pertaining to the present invention has beendesigned such that each component of the blister package and the gearmechanism which have a significant role in enabling the device to workproperly is situated accurately and works harmoniously. To this end, thehousing is divided into several compartments. The used portion and theunused portion of the blister package are accommodated in separatedcompartments in order to prevent the residual dry powder medicament inthe opened blister pocket spilling on the other components of thehousing. Furthermore, the housing also comprises a beak which enablesthe blister package to be peeled and a manifold through which the drypowder medicament in the open blister pocket passes before reaching themouthpiece during the inhalation. The housing can be in any appropriateshape through it is preferably elliptic or circular.

The inhaler (1) pertaining to the present invention comprises a gearmechanism situated in the housing (10) between the upper housing member(4 a) and the lower housing member (4 b) in order to enable theinhalation of the dry powder medicament carried in a blister package(15) as displayed in FIGS. 1 a and 2 a. Each component of the inhaler(1) is positioned at suitable spots on the housing (10) to guaranteetheir working properly and accurately. The cross-sectional view A-A inFIG. 1 c and the cross-sectional view B-B of FIG. 1 d clearly displaythe communication of the gear mechanism with the other components of theinhaler (1) and their locations.

The inhaler (1) pertaining to the present invention shown in FIGS. 1 aand 2 a is ready for inhalation. In this case, the mouthpiece cover (2)is in the second position and the mouthpiece (14) is entirely exposed.The mouthpiece cover (2) has to be rotated by holding on the carved part(2 a) on one end of the mouthpiece cover (2) in order to switch to thesecond position from the first position wherein the mouthpiece iscompletely covered. In this way, the mouthpiece (14) is completelyexposed when the mouthpiece cover (2) is switched to the second positionfrom the first position and the gear mechanism is triggered by the drivegear (12). The drive gear (12) precisely transmits the movement of themouthpiece cover (2) to the indexing ratchet wheel (3).

The indexing wheel (8) which engages with the indexing ratchet wheel (3)enables the blister package (15) shown in FIG. 3 to be indexed. Theblister pockets (15 a) composing the blister package are received in therecesses (8 a) on the indexing wheel and the blister package (15) isindexed when the indexing wheel (8) rotates. In the inhaler pertainingto the present invention, shapes of the recesses (8 a) on the indexingwheel (8) have been designed to match the shapes of the blister pockets(15) composing the blister package (15) for the blister package to beindexed properly.

The movement of the indexing wheel (8) is transmitted to the base gear(7) engaging with the pinion gear (11) by the pinion gear (11). Thesmall gear which is under the base gear (7) and attached to it engageswith the counter gear (9). Thus, the movement of the indexing wheel (8)is transmitted to the counter gear (9) shown in FIG. 13 by the piniongear (11) and the base gear. There are numerals incrementing from 1 to60 in the counter gear (9) displayed in FIG. 13. The angles betweenthese numerals are all equal and approximately 5 degrees. The movementof the indexing wheel (8) by 45 degrees in response to each actuation ofthe device causes the counter gear to move approximately 5 degrees andthe number of the unused blister pockets remained in the device to beclearly seen through the display aperture (4 c) on the lower housingmember (4 b).

The blister package (15) shown in FIG. 3 is composed of the lid sheet(15 b) which provides impermeability and the base sheet (15 c) on whichthe blister pockets (15 a) are spaced at equal intervals. Each blisterpocket contains medicament in dry powder form comprising one or moreactive agents.

The rotational movement that the mouthpiece cover (2) of the deviceexecutes while switching from the first position to the second istransmitted to the indexing ratchet wheel (3) via the drive gear (12)that the mouthpiece cover (2) engages with. As displayed in FIG. 2 a,arms (3 a) of the indexing ratchet wheel interlocks with protrusionsinside the indexing wheel (8) and rotates the indexing wheel (8)unidirectionally. Therefore, the blister package (15) is indexed forwardwhile the indexing wheel (8 a) rotates as the blister pockets (15 a)composing the blister package (15) are received in the recesses (8 a) ofthe indexing wheel. The beak (16) in the housing (10) provides theblister package (15) to be peeled while the blister package (15) isindexed and provides one blister pocket (15 a) to be opened in responseto each actuation of the device (1).

The winding wheel gear (6), which is another component of the gearmechanism, engages with the indexing wheel (8) as displayed in FIG. 2 a.The mechanism gear (5) that interlocks with the winding wheel (13) frominside has arms (5 a) to interlock with the interior teeth of thewinding wheel gear (6). When the indexing wheel (12) rotates the windingwheel gear (6), the winding wheel rotates unidirectionally owing to thearms of the mechanism gear (5 a) which interlocks with the interiorteeth of the winding wheel gear (6) and the lid sheet (15 b) which ispeeled away while the blister package is indexed is tightly coiled onthe resilient wings (13 a) of the winding wheel. The base sheet (15 c)of the blister package (15) where the blister pockets are spaced isaccumulated in a separate part (18 a) of the device (FIG. 4 j). Eachresilient wing (13 a) of the winding wheel extends from the center ofthe winding wheel (13) to the end.

As illustrated in FIG. 12, the winding wheel (13) of the inhalerpertaining to the present invention is composed of a plurality ofresilient wings which are preferably made of polyoxymethylene plastics.Each of these resilient wings (13 a) is composed of three parts (A, B,C) each of which has different radius values. Thus, these resilientwings (13 a) stretch enough to balance the force of attraction imposedon the lid sheet (15 b) of the blister package, therefore on the blisterpackage (15), as the thickness of the lid sheet (15 b) of the blisterpackage coiling on them increases, and they enable the blister package(15) to be indexed properly to the same extent in response to eachactuation of the inhaler. The resilient wings of the winding wheelillustrated in FIG. 12 are composed of 3 parts (A; B; C). The averageradius (R1) of the second part (B) of each resilient wing is in therange of 4.60 mm to 5.20 mm, preferably in the range of 4.75 mm to 5.15mm; and the radius (R2) of the piece of the third part (C) that curlsthrough the end of the resilient wing is in the range of 0.9 mm to 1.70mm, preferably in the range of 1.10 mm to 1.50 mm.

Different views of the housing (10) wherein the gear mechanism and theother components of the inhaler (1) pertaining to the present inventionare arranged are displayed in FIGS. 4 a and 4 b. Furthermore, as can beseen in FIGS. 4 a through 4 j, the housing (10) also comprises thecomponents having significant roles in the actuation of the device suchas the beak (16), the manifold (20), the apertures with foursub-apertures (20 a, 20 b). Each component comprised in the housing issituated in appropriate parts of the housing (10) in order to enable theinhaler (1) to work properly. The drive gear (12) passes through thecenter (21) of the housing and joins the mouthpiece cover (2) at bothsides of the inhaler. The blister package (15) is in the lower part (17)of the housing as coiled up. In response to each actuation of the device(1), the blister package (15) is peeled by the beak (16) in the housingwhile being indexed by the indexing wheel (8) situated in the upper part(19) of the housing. The lid sheet (15 b) of the blister package (15)which provides impermeability is indexed over the beak (16) and coiledon the winding wheel (13) which is situated in the side part (18) of thehousing. The base sheet (15 c) of the blister package (15) on which theblister pockets (15 a) are spaced, on the other hand, is accumulated inthe separated compartment (18 a) of the housing (10). Upon theinhalation of the patient, the air passes through the air inlet withfour sub-apertures (20 a) under the manifold (20) into the openedblister pocket; entrains the dry powder medicament contained in theopened blister pocket (15 a) in response to each actuation of thedevice; provides it to pass through the other aperture withfour-sub-apertures (20 b) and reach the mouthpiece via the manifold(20).

The housing (10) and the other components of the inhaler (1) pertainingto the present invention are stably kept together as the upper housingmember (4 a) and the lower housing member (4 b) displayed in FIGS. 5 athrough 5 h are joined together. The engagement tabs (28) on the insidesurface of the lower housing member (4 b) engage with the engagementrecesses (27) on the inside surface of the upper housing member (4 a)and the upper and lower housing members are fixed tightly. Therefore,the protrusions (23 a, 23 b) on the upper housing member (4 a) and theprotrusions (24 a, 24 b) on the lower housing member (4 b) are joinedend to end and they define the restricted path for the rotationalmovement of the mouthpiece cover (2). The mouthpiece cover (2) can bemoved along this path. When the mouthpiece cover (2) is on the firstposition, the mouthpiece is completely covered, the device is in standbymode and the mouthpiece cover (2) leans on the first protrusion (23 a)on the upper housing member and the first protrusion (24 a) on the lowerhousing member. The mouthpiece (2) is manually slid along the rotationalpath with the help of the carved part to switch to the second position.The mouthpiece is completely exposed when the cover is in this position,one dose of the dry powder medicament is ready for inhalation and themouthpiece cover (2) leans on the second protrusion (23 b) on the upperhousing member and the second protrusion (24 b) on the lower housingmember.

A view of the cross-section of the housing component (10) whichillustrated as X in FIG. 4 c and includes the manifold part (20) isgiven in FIGS. 4 e and 4 f. According to FIG. 4 e, the blister pocket(15 a) opened upon the actuation of the inhaler (1) is positionedimmediately under the apertures with four sub-apertures (20 a, 20 b).There are two apertures with four sub-apertures (20 a, 20 b) on the edgeof the manifold (20) which is close to the blister (15 a) and they arepartitioned off from each other by a wall. This wall is named as wall Ain FIG. 4 c and it partitions the manifold (20) into two parts. Wall Alies between the first part (20 c) and the second part (20 d) of themanifold and it belongs to both the first part (20 c) and the secondpart (20 d) of the manifold. Upon the respiration of the patient so asto inhale the medicament in dry powder form in the opened blister pocket(15 a), the external air that enters the inhaler passing through the airinlet (22) on the upper housing member reaches the first part (20 c) ofthe manifold. Some part of this airflow reaches the opened blister (15a) by passing through the aperture with four sub-apertures (20 a) on theedge of the first part of the manifold. The airflow reaching the openedblister pocket (15 a) entrains the dry powder medicament in the blisterto the second part (20 d) of the manifold through the other aperturewith four sub-apertures (20 b) on the edge of the manifold which isclose to the blister. Wall A and wall B shown in FIG. 4 c are twoopposite walls in the second part (20 d) of the manifold. Some part ofthe external air which runs through the air inlet (22) and enters theinhaler (1) upon the patient's breathing in passes through the firstpart (20 c) of the manifold and reaches the opened blister pocket (15 a)while the rest passes through the aperture (20 e) on wall A and theaperture (20 f) on wall B and enters the second part (20 d) of themanifold. The apertures (20, 20 f) on wall A and wall B areasymmetrically positioned. Shapes and the cross-sections of theapertures (20 e, 20 f) on wall A and wall B can be identical ordifferent. Thus, an effective turbulence is created in the second part(20 d) of the manifold as the speed of the airflow entering through theaperture (20 e) on wall A and the speed of the airflow entering throughthe aperture (20 f) on wall B are different. The created turbulencedisperse the agglomeration of the dry powder medicament entrained to thesecond part (20 d) of the manifold and provides the dry powdermedicament to be delivered to the patient at appropriate particle sizedistribution.

Another cross-sectional view of the part of the housing which is shownas X in FIG. 4 c is given in FIG. 4 f. In the cross-sectional view ofthe manifold illustrated in FIG. 4 f, there are two apertures (20 f, 20g) on wall B of the manifold differently from FIG. 4 e. The apertures(20 e, 20 f) on wall A and wall B are asymmetrically positioned withrespect to each other. The shapes and the cross-sections of theapertures (20 e, 20 f, 20 f) on wall A and wall B which allow the air inthe second part (20 d) of the manifold can be identical or different.Thus, the airflow entering in through the aperture (20 e) on wall A andthe airflows entering in through the apertures (20 f, 20 g) on wall Bcreate an effective turbulence in the second part (20 d) of themanifold. This turbulence disperses the agglomeration in the dry powdermedicament entrained to the second part (20 d) of the manifold andenables the medicament in dry powder form to be delivered to the patientat an appropriate particle size distribution.

The drive gear (12) passes through the aperture (4 d) in the center ofthe upper housing member displayed in FIGS. 5 e and 5 f and the aperture(4 e) in the center of the lower housing member, then it is joined withthe mouthpiece cover (2) on two ends. There is a tapered channel betweenthe manifold (20) and the mouthpiece (14). As displayed in FIGS. 5 c and5 d, one half (25 a) of the tapered channel that interconnects themanifold (20) that exist in the housing (10) with the mouthpiece (14) iscomprised in the upper housing member (4 a) while the other half of it(25 b) is comprised in the lower housing member (4 b). The channel isconstituted as a whole when the upper (4 a) and the lower (4 b) housingmembers are joined together. Upon the inhalation of the patient, the airthat enters the device through the air inlet (22) arranged in the upperhousing member (4 a) passes through the aperture with four sub-apertures(20 a), reaches the opened blister (15 a) and entrains the dry powdermedicament there to the manifold (20) by passing it through the otheraperture with four sub-apertures (20 b). The grids on the upper housingmember (23 e, 23 f) and the grids on the lower housing member (24 e, 24f) prevent the slips of fingers when rotating the mouthpiece cover.

The mouthpiece cover (2) of the inhaler pertaining to the presentinvention is displayed in FIGS. 6 a through 6 f. The carved part, whichis the finger tab (2 a) in one end of the device enables the mouthpiececover to be easily removed manually as seen in FIG. 6 d. The finger tab(2 a) has been designed to match the finger shape and is situated in anysuitable spot on the mouthpiece cover (2). As can be seen clearly inFIGS. 6 c and 6 d, the first and the second connection points (29, 30)of the mouthpiece cover have recesses (29 a, 30 a) on their insidesurfaces. Protrusions (31 a, 31 b) on the two ends of the drive gear(12) displayed in FIGS. 7 e and 7 f make a male-female connection withthese recesses (29 a, 30 a). The first recess (30 a) on the insidesurface of the mouthpiece cover engages with the first protrusion (31 a)on the one end of drive gear while the second recess on the insidesurface of the mouthpiece cover (29 a) engages with the secondprotrusion (31 b) on the other end of the drive gear and the connectionprovided between each end of the drive gear (31 a, 31 b) and thecorresponding recess (30 a, 29 a) on the inside surface of themouthpiece cover is a male-female connection. The male-female connectionthat each end of the drive gear (31 a, 31 b) makes with thecorresponding recessed parts on the inside surface of the mouthpiececover (30 a, 29 a) causes to form an inside lock connection between thedrive gear (12) and the mouthpiece gear (2) with maximum ±0.01% marginof error. Therefore, the rotational movement of the mouthpiece cover (2)on the upper (4 a) and lower (4 b) housing members is accuratelytransmitted to the indexing ratchet wheel by the drive gear (12) whichhas an inside lock connection with the mouthpiece (2) on its two ends.

The mouthpiece cover (2) is joined with the gear mechanism via theconnection points. The drive gear consists of two ends (12 a, 12 b) anda hole (12 c) at the center of one end as seen in FIG. 7 g. Further, thedrive gear (12) is joined with the connection points (29, 30) of themouthpiece cover via the side covers (31 a, 31 c) as it can clearly beseen in FIGS. 6 e, 6 h, 6 i and 6 j illustrating the communicationbetween the mouthpiece cover (2), the drive gear (12), side covers (31a, 31 c) and the stabilizing resilient covers (32,33). Each of theseside covers (31 a, 31 c) passes through the center (4 d) of the upperhousing member or the center (4 e) of the lower housing member and joinswith the end (12 a, 12 b) of the drive gear. It can clearly be seen inFIG. 6 j that the both ends (12 a; 12 b) of the drive gear are carvedsuch that the end of the side cover (31 b, 31 d) can pass through. Theend of the drive gear (12 a) that is fixed into one connection point ofthe mouthpiece cover (29) has a hole (12 c) at the center. In addition,each of the connection points (29, 30) itself is a hole in shape (FIG. 6b). Therefore, the end of the drive gear (12 a) is fixed into theconnection point of the mouthpiece cover (29) while the extension part(33 c) present at the centre of the inside surface of the protectivecover is fixed into both the hole (12 c) at the centre of said end ofthe drive gear and the connection point of the mouthpiece cover.

The shape of one of the connection points of the mouthpiece cover (29)is different from the shape of the other connection point of themouthpiece cover (30) as well as the shape of the end of the drive gear(12 a) that is connected with one connection point of the mouthpiececover (29) is different from shape of other end of the drive gear (12 b)(FIGS. 6 b, 7 f and 7 g).

Each end of the side covers (31 d, 31 b) passes through one of theconnection points (29, 30) of the mouthpiece cover and it is received inthe recess in one end (12 b, 12 a) of the drive gear, thus it providesto tightly and stably interconnect the mouthpiece cover (2) with thedrive gear (12). It is provided that the mouthpiece cover (2)synchronizes with the drive gear (12) as the connection point (29, 30)of the mouthpiece cover which has a matching shape with the ends (31 d,31 b) of the side covers that passes through it on both sides of thedevice and the end (12 b, 12 d) of the drive gear that it communicateswith are on the same component.

As is seen from FIGS. 6 a through 6 j, and 7 h, the shapes of the ends(31 b; 31 d) of the side covers that are received in the carved parts onthe ends of the drive gear and the shapes of the connection points (29,30) of the mouthpiece cover are not identical since the two ends (12 a,12 b) of the drive gear are not identical.

The mouthpiece cover (2) rotates by the same angle each time it isswitched from the first position to the second position on the pathrestricted by the protrusions (29 a, 29 b, 30 a, 30 b) on the upper andthe lower housing members (4 a, 4 b). The rotational angle of themouthpiece cover (2) varies depending on the shape and the size of thedevice but is a fixed value between 30° and 160°. This angle is adjustedaccording to the shape and the size of the device such that the indexingwheel (12) having 8 recesses (8 a) rotates 45 degrees in response toeach actuation of the device. The mouthpiece cover (2) rotates by thesame angle on its two ends in response to each actuation of the deviceand this rotational movement of the mouthpiece cover (2) is accuratelytransmitted to the indexing wheel (12) by the indexing ratchet wheel (3)because of the drive gear (12) which is tightly attached to themouthpiece cover (2) and the indexing wheel is provided to rotate 45°each time the device is triggered.

The mouthpiece cover (2) can be rotated by holding from the front end (2a) or back end (2 b) of its with the help of the thumb. Therefore, thefront end (2 a) or the back end (2 b) of the mouthpiece cover (2) is incontact with the patient's finger while it is moved manually. Accordingto FIG. 2 c, only the front end (2 a) of the mouthpiece cover (2) of theinhaler is carved such that it matches with the shape of the thumb so asto provide the mouthpiece cover (2) to be rotated easily and rapidlywhile the back end (2 b) of the mouthpiece cover is not carved. However,it is probable that both the front end (2 a) and the back end (2 b) ofthe mouthpiece cover are carved. The shape of the carved part in thefront end (2 a) of the mouthpiece cover resembles to the shape of thethumb for the thumb to be placed in this carved part exactly in order torotate the mouthpiece cover. Thus, the carved part of the front end (2a) of the mouthpiece cover illustrated in FIG. 2 c is in the shape ofthe arc of the circle which has a radius (R) in the range of 30 mm to 40mm, preferably in the range of 32.5 mm to 37.5 mm. In more detail, thecarved part (2 a) in the front end of the mouthpiece of the device shownin FIG. 2 c is in the shape of the arc of 45° of said circle.

The mouthpiece cover that triggers the gear mechanism of the device canbe found in two positions. When the mouthpiece cover is in the firstposition, the mouthpiece cover resides on the protruding part on one endof the rotational path. When the first position is on, the mouthpiececover is completely covered and the device is in standby mode. When themouthpiece is in the second position, it resides on the protruding parton the other end of the rotational path and one dose of the dry powdermedicament becomes ready for inhalation upon the actuation of thedevice.

According to the present invention, there preferably exists a finger tabon the device cover. The word “finger tab” refers to the component thatenables the patient to slide the cover comfortably.

Each gear of the gear mechanism in the device according to the presentinvention directly or indirectly engages with each other. The drivegear, which is one of the components of the gear mechanism, provides themouthpiece cover to trigger the gear mechanism in such a way that thetwo ends of the drive gear which engage with the recessed parts on theinside face of the mouthpiece cover through a male-female connectionenable an inside lock connection to be provided between the mouthpiececover and the drive gear. One of the recesses on the inside surface ofthe mouthpiece cover engages with the one end of drive gear while theother recess on the inside surface of the mouthpiece cover engages withthe other end of the drive gear and the connection, that is providedbetween the each end of the drive gear and the corresponding recess onthe inside surface of the mouthpiece cover, is a male-female connection.

As regards the other components of the gear mechanism, in each actuationof the device, the constant-angle rotational movement of the cover istransmitted by the indexing ratchet wheel which interlocks with theindexing wheel via the drive gear. The indexing wheel synchronizes withthe indexing ratchet wheel when the mouthpiece cover is switched fromthe first position to the second position. The gear of the indexingwheel is engaged with the winding wheel gear and the pinion gear and therotation of the indexing wheel gear causes them to move as well. Themechanism wheel engages with the winding wheel gear via its arms. Thecounter gear that engages with the small gear under the base gearrotates by means of the base gear that engages with the pinion gear andcounter gear with movement of the mouthpiece cover. Therefore, with therotation of the indexing wheel, both the lid sheet of the blisterpackage is provided to be coiled on the wings of the winding wheel asthe winding wheel is rotated by the mechanism wheel that engages withthe winding wheel gear, and the counter gear that engages with the smallgear under the base gear rotates by means of the base gear that engageswith the pinion gear. After the counter gear is rotated, the new numberof unused blister pockets can be seen through the display aperture.According to the present invention, the mouthpiece cover triggers thegear mechanism via the drive gear. Therefore, the rotation of themouthpiece cover has to be transmitted to the drive gear precisely inorder to prevent uncontrolled dosing resulting from the mispositioningof the blister package when the device is triggered. In an inhalationdevice comprising a blister package which has a gear mechanism triggeredby the mouthpiece cover, it is required that the rotation of themouthpiece cover is transmitted to the gear mechanism with minimummargin of error for the blister package to be accurately positioned.

According to the present invention, the mouthpiece cover, whose recessedparts on the inside surface of said mouthpiece cover engage with the twoends of the drive gear through a male-female connection such that theinside lock connection is provided between the mouthpiece cover and thedrive gear. In each actuation of the inhalation device, the gearmechanism is triggered by the rotational movement of said mouthpiececover from the first position to the second position along therotational path restricted on both ends by the protruding parts on theupper and the lower housing members to provide the blister package to beadvanced. In each actuation of the device, the constant-distance paththat the protrusions of the upper and the lower housing members defineallows said mouthpiece cover to be rotated by a fixed angle.Accordingly, because of the inside lock connection provided between themouthpiece cover and the drive gear, in each actuation of the inhalationdevice, only rotation of said mouthpiece cover from the first positionto the second position on the constant-distance path guarantees that theblister package is advanced by the same distance and the opened blisteris at accurate position so that the sufficient amount of the dry powderformulation contained in the opened blister can be inhaled. In additionto this, the patient can make sure about whether the blister is openedcompletely by controlling the position of the mouthpiece cover on theconstant-distance path. In other words, if the mouthpiece cover is inthe second position wherein it resides on the protruding part on theother end of the constant-distance rotational path, the patient makessure that one blister is completely opened and one dose of the drypowder medicament contained in the opened blister becomes ready forinhalation; if the mouthpiece cover is between the first position andthe second position, the patient makes sure about that one blister isnot completely opened.

Two ends of the drive gear has been designed such that they form aninside lock connection with the mouthpiece cover. The inside lockconnection between the two ends of the drive gear is formed preferablyby male-female connections on the both sides. According to the presentinvention, due to this inside lock connection, the rotational movementof the mouthpiece cover is transmitted to the gear mechanism withminimum margin of error for the blister package to be accuratelypositioned. Therefore, the rotational movement of the mouthpiece coverhas to be transmitted to gear mechanism exactly in order to preventuncontrolled dosing resulting from the mispositioning of the blisterpackage when the inhalation device is actuated. The mouthpiece cover andthe drive gear synchronize with maximum ±0.01% margin of error thanks tothe inside lock connection between the mouthpiece cover and the drivegear. This rate of margin of error resulting from the connection betweenthe mouthpiece cover and the drive gear enables each blister pocket fromthe first one to the last to be opened completely because the precisepositioning of the blister package is based on exact transmission of themovement of the mouthpiece cover to the other components in aninhalation device triggered by the mouthpiece cover. Accordingly, thedrive gear, which has an inside lock connection with the mouthpiececover, transmits the movement of the mouthpiece cover that rotates bythe same angle in each inhalation to the indexing wheel via an indexingratchet wheel interlocked into an indexing wheel and enables the blisterpackage to be indexed properly and the opened blister pocket to bepositioned accurately in the device pertaining to the present invention.

According to the present invention, the indexing wheel can be anothercomponent of the gear mechanism. As a result of the transmission of therotation of the mouthpiece cover to the gear mechanism via the drivegear with ±0.01% margin of error, the blister pockets are received inthe recesses of the indexing wheel, the blister package is indexedproperly and the opened blisters are accurately positioned. The recessesof the indexing wheel match with the shape of the blister package.Blister pockets of the blister package are received in these recesseswhile the indexing wheel rotates. The rotation angle of the indexingwheel depends on the number of the recesses of the indexing wheel. Ineach actuation of the inhalation device, the indexing wheel can berotated by an angle of 15° to 120°. According to the invention, thereare preferably 8 recesses of the indexing wheel. Therefore, the indexingwheel is supposed to rotate 45 degrees when the device is actuated forthe blister to be positioned accurately. In the device pertaining to thepresent invention, the rotational movement of the mouthpiece cover whichis fixed at a value between 30° and 160° is transmitted to the indexingwheel with ±0.01% margin of error owing to the connection between themouthpiece cover and the drive gear whenever the device is actuated.Therefore, the indexing wheel rotates 45 degrees whenever the device isactuated. As the indexing wheel rotates 45 degrees whenever the deviceis actuated, the blister package is accurately positioned and controlleddosing of the medicament in dry powder from is provided.

At least one component may be situated on the lower housing member andserves as a stopper interlocks with the tooth of at least one of thegears of the gear mechanism and stabilizes the gear in a suitableposition in order to prevent backward rotation of the blister packageand enables it to be precisely positioned. While the stopper can hinderthe rotation of any gear of the gear mechanism, it preferably hindersthe rotation of the indexing ratchet wheel interlocked in the indexingwheel. The stopper can be anywhere suitable in the lower housing memberand have any shape.

The counter gear in the device pertaining to the present invention maydisplay the number of the unused blister pockets remained in the device.In response to the actuation of the device by the mouthpiece cover, themouthpiece is uncovered, the blister package is indexed and one dose ofthe dry powder medicament is prepared for inhalation while the countergear rotates as well. Thus, the movement of the mouthpiece cover leadsto the mouthpiece being exposed; one dose of the dry powder medicamentto be ready for inhalation after the blister pocket is opened as well asproviding the counter gear to rotate and display the new value of theremaining unused blister pockets through the display aperture.

On the counter wheel, there exist numerals equal to the number of theblister pockets present in the device and they are spaced by equalangles. In a device comprising 60 doses, the angle between the numeralsis approximately 5 degrees. The counter gear rotates as a result of thereflection of the rotation of the indexing wheel gear via the piniongear and the base gear. In response to the each actuation of the device,rotation of the indexing wheel by the same angle each time due to theaccurate transmission of the movement of the mouthpiece cover to thegear mechanism via the drive gear results in the rotation of the countergear approximately by the same angle as well, and each numeral on thecounter wheel is clearly seen through the display aperture on the upperhousing member. Therefore, the patient is sure about the number of theunused blister pockets remaining in the device.

The inhaler according to the present invention comprises a blisterpackage composed of a plurality of blister pockets each of whichcomprises medicament in dry powder form and which are spaced at equalintervals. The blister package carries the medicament in dry powder formin one-dose portions and it is preferably a blister strip and it ispreferably peelable. The blister pockets comprised in the blisterpackage are spaced in equal intervals and each of them carries one doseof the medicament in dry powder form. While the blister package isindexed on the indexing wheel, the beak on the housing peels theblister. Therefore, one dose dry powder medicament becomes ready forinhalation after the blister package is peeled open in each actuation ofthe device.

According to another aspect, the blister opened by the beak may besituated immediately under a manifold. The airflow that enters thedevice through at least one air inlet on the upper housing memberentrains the dry powder medicament in the opened blister pocket via themanifold to the mouthpiece and enables the delivery of said medicamentto the patient. The air inlet on the upper housing member that allowsthe entry of air can be in any suitable shape and size that enablesexternal air to enter the device easily and at a convenient speed.

The air inlet that the external air flow passes through is designed notto be close where the patient holds the device in order not to preventair flow. Furthermore, in order to deliver the required amount of thedry powder medicament in the opened blister to the patient, the airinlet is designed such that it allows the entry of the airflow throughthe air inlet at a convenient angle.

The lid and the base sheets constituting the blister package preferablyconsist of a plurality of layers. These layers are preferably chosenfrom a group comprising polymeric layers that are made of polymericsubstances, aluminum foil and fluoropoylmer film.

According to the present invention, the lid and base sheets forming theblister package are sealed very tightly by at least one of the methodspreferably comprising cold formed bonding, hot metal bonding, hot metalwelding, radio frequency welding, laser welding or ultrasonic welding inorder to provide impermeability, more preferably by cold formed bondingmethod. Since these cold formed bonding methods can be carried out atlower temperatures than hot sealing methods, they are the mostappropriate methods to use in the case that the medicament carried inthe blister is heat sensitive.

Fluoropolymer film is a polymeric film which is used in blister packsand provides an excellent moisture barrier. This chemically inertpolymeric film does not cause any change in the taste of the formulationwhen it is in contact with the dry powder formulation. In addition, iteasily constitutes a layered structure with the other polymeric layerswhich are composed of various polymers. It is appropriate to betransacted with heat.

For preserving the stability of the dry powder formulation stored in theblister package, preferably at least one of the polymeric layerscomprises at least one desiccant agent including silica gel, zeolite,alumina, bauxite, anhydrous calcium sulfate, activated carbon and claywhich has the property of water absorption in order to decrease gas andmoisture permeability of the layer.

In order to provide high moisture and gas protection, aluminum foil canbe used in the lid and base sheets of blister packs. This aluminum foilmust be thick enough to provide the desired protection for the stabilityof the moisture sensitive dry powder formulation stored in the blistercavity and it may be preferably in the range of 5 to 80 μm, morepreferably in the range of 15 to 65 μm.

The polymeric layers in the lid and the base sheets of the blister packmentioned in the present invention are made of the same or differentpolymers. The thickness of these polymeric layers varies according tothe type of the polymeric substance used and its properties and arepreferably in the range of 5-100 μm, more preferably in the range of15-60 μm.

The polymers composing the polymeric layer are preferably selected fromthermoplastics such as polyethylene, polypropylene, polystyrene,polyolefin, polyamide, polyvinyl chloride, polyurethane or syntheticpolymers.

The blister pockets in the blister package can be in any appropriateshape. The plurality of blister pockets spaced at equal intervals on thebase sheet of the blister package can be in the same or different shape,structure or volume.

In addition, another variable contributing to the carved part in thefront end (2 a) of the mouthpiece cover to match with the shape of thethumb is the width of the mouthpiece cover (2) illustrated as D1 in FIG.2 d. For the thumb to be able to grip the cover and impose force, aparticular part has to be in contact with the carved part in the frontend (2 a) and the back end (2 b) of the mouthpiece cover. To this end,D1 distance is in the range of 10 mm to 20 mm, preferably in the rangeof 11 mm to 16 mm.

There are 8 recesses (8 a) on the indexing wheel displayed in FIG. 2 aand the indexing wheel (8) rotates 45° each time for the blistersreceived in these recesses to be able to be positioned accurately. Theblister package (15) is indexed by the 45° rotation of the indexingwheel (8) in response to each actuation of the device and is peeled bythe beak (16) so one dose of the dry powder medicament becomes ready forinhalation when one blister pocket is opened. As seen in FIG. 8, the lidsheet (15 b) that is peeled away by the beak (16) and the base sheet (15c) of the blister package (15) are enclosed in separate compartments.The lid sheet (15 b), which provides impermeability of the blisterpackage, passes over the beak (16) and tightly coils on the wings (13 a)of the winding wheel. The base sheet (15 c) with blister pockets (15 a),each of which comprises one dose of the dry powder medicament, isaccumulated in the separated compartment (18 a) in the housing (10). Inresponse to each actuation of the device (1), one dose of the dry powdermedicament becomes ready for inhalation after one blister pocket (15 a)is opened; the air which enters the device through the air inlet (22)upon the inhalation of the patient entrains the dry powder medicament tothe mouthpiece and provides to deliver it to the patient.

There is at least one stopper (26) in the lower housing member displayedin FIG. 6 a in order to provide the opened blister in the blisterpackage (15) which is indexed by the indexing wheel (8) so as to bepositioned accurately. This stopper (26) engages with the tooth of atleast one gear and provides the position of this gear to stay immovableand the opened blister to be accurately positioned. This stopper (26)can be any suitable shape and size according to the structure of thegear it stops.

There is one stabilizing resilient cover (33; 32) on each connectionpoint (29; 30) of the mouthpiece and on each side cover (31 c; 31 a), asdisplayed in FIGS. 2 a, 6 a, 6 h-6 j and 5 i. When the mouthpiece cover(2) is in the first position, the pawls (32 a, 33 a) under thestabilizing resilient covers, which are on the connection points (29,30) of the mouthpiece, interlock with the mouthpiece cover (2) on bothsides as clearly seen in FIGS. 6 i and 6 j. The pawl (33 a) under thestabilizing resilient cover that is on the first connection point (29)interlocks with the mouthpiece cover on one side (FIG. 6 i).Identically, the pawl (32 a) under the stabilizing resilient cover thatis on the second connection point (30) of the mouthpiece coverinterlocks with the mouthpiece cover (2) on the other side (FIG. 6 j).Thus, these pawls (32 a, 33 a) under the stabilizing resilient coversprevent the movement of the mouthpiece cover (2) by interlocking with iton both sides.

The extensions (32 b, 32 c, 33 b, 33 c) under the stabilizing resilientcovers pass through the apertures (23 c, 23 d, 24 c, 24 d) on the upperand the lower housing members illustrated in FIGS. 5 a and 5 b andprovide the stabilizing resilient covers to remain stable. Namely, theextensions (33 b, 33 c) under the stabilizing resilient cover that is onthe first connection point (29) of the mouthpiece cover pass through theapertures (23 c, 23 d) on the upper housing member and provide thestabilizing resilient cover (33) to be stably joined with the device.Identically, the extensions (32 b, 32 c) under the stabilizing resilientcover on the second connection point (30) of the mouthpiece cover passthrough the apertures (24 c, 24 d) on the lower housing member andprovide the stabilizing resilient cover (32) to be stably joined withthe device as clearly illustrated in FIG. 5 i.

Before the inhalation, the resilient parts (32 d, 33 d) of eachstabilizing resilient cover illustrated in FIGS. 6 i and 6 j are pressedon for raising the pawls (32 a, 33 a) and releasing the mouthpiece cover(2) in order to actuate the gear mechanism of the device to prepare onedose of dry powder medicament before inhalation. Therefore, the gearmechanism of the device is actuated and one blister pocket (15 a) isopened for one dose of the dry powder medicament to be ready forinhalation when the resilient parts (32 d, 33 d) of the stabilizingresilient covers are pressed on and the mouthpiece cover (2) is switchedfrom the first position to the second position simultaneously. Thenecessity to press on the resilient parts (32 d, 33 d) of thestabilizing resilient covers so as to actuate the gear mechanismpreclude the consequences which may result from accidental andinadvertent actuations of the gear mechanism.

The inhaler (1) of the present invention has a stopper (31) that issituated between the lower housing member (4 b) and the housing (10) asengaging with the two holes on the lower housing member (4 b) (FIGS. 5 dand 6 a). The stopper is shown in FIGS. 10 a and 10 b. This stopper (31)consists of a pawl (31 a), a pressing button (31 b), and a supportingpart (31 c). Each of the pawl (31 a) and the pressing button (31 b)situated in one hole of the lower housing member (4 b) and is shown fromthe outside as the supporting part (31 c) is situated at the inside ofthe inhaler and is not shown from the outside (FIGS. 4 i and 6 a). Foractuation of the inhaler, the mouthpiece cover (2) is switched from thefirst position to the second position over the rotational path. However,the pawl (32 a) is engaged to the recess part (2 c) on inside surface ofthe mouthpiece cover (2) to prevent the movement of the mouthpiece cover(2) when the mouthpiece cover (2) is in the first position in which themouthpiece (14) is completely covered. Since the pressing button (31 b)moves synchronously with the pawl (31 a), when the pressing button (31b) is pressed, the pawl (31 a) is advanced forward inside of the inhalerand disengaged from the mouthpiece cover (2). After the pawl (31 a) isdisengaged from the mouthpiece cover (2), the mouthpiece cover (2) canbe rotated from the first position to the second position to actuate theinhaler.

Because of the supporting part (31 c) of the stopper, there is no needfor a spring to enable the pressing button (31 b) to be pressed. Thereis an end (31 d) that is integrated with the supporting part and leansthe housing of the inhaler. When the pressing button is pressed, thesupporting part springs over the end of said supporting part (31 d) andboth of the pressing button (31 b) and the pawl (31 a) are advancedforward inside of the inhaler.

The inhaler has another stopper (26) in the lower housing member (4 b)in order to provide the opened blister in the blister package (15) whichis indexed by the indexing wheel (8) to be positioned precisely. FIGS. 7a, 7 b, and 11 show that the stopper (26) interlocks with the tooth ofthe indexing wheel (8) and hinders its rotation. The rotational movementof the mouthpiece cover (2) by the same angle each time the device (1)is actuated is precisely transmitted to the indexing ratchet wheel (3)by the drive gear (12) that joins with one connection point (29) of themouthpiece cover, and therefore the indexing wheel (8) which engageswith the indexing ratchet wheel (3) is rotated by the same angle eachtime the device (1) is actuated. The stopper component (26) positionedin the lower housing member (4 b) prevents backward movement of theblister package (15) which is indexed by the indexing wheel (8) thatsynchronizes with the indexing ratchet wheel (3) by keeping the positionof the indexing wheel (8) stable and provides the blister package (15)to be precisely positioned.

As can be seen in FIGS. 7 a through 7 c, the indexing wheel (8) whichsynchronizes with the indexing ratchet wheel (3) is engaged with thewinding wheel gear (6) and the pinion gear (11) and the rotation of theindexing wheel (8) causes the pinion gear (11) and the winding wheelgear (6) to rotate. Thus, both the peeled lid sheet (15 b) of theblister package (15) which is indexed by the rotation of the indexingwheel (8) is tightly coiled on the winding wheel (13) engaging with thewinding wheel gear (6) and also the counter wheel (9) is provided to bemoved by the pinion gear (11) and the base gear (7) as a result of therotation of the indexing wheel (8).

The rotation of the indexing wheel (8) is transmitted to the base gear(7) engaging with the pinion gear (11) by the pinion gear (11). Thesmall gear which is under the base gear (7) as attached engages with thecounter gear (9) (FIG. 7 b). Thus, the movement of the indexing wheel(8) is transmitted to the counter wheel (9) shown in FIG. 9 by thepinion gear (11) and the base gear. There are numerals incrementing from1 to 60 in the counter gear displayed in FIG. 9. In response to eachactuation of the device, the counter gear rotates approximately 5° andthe number of unused blister pockets remained in the device are seenthrough the display aperture (4 c) on the lower housing member (4 b).

In use of the device described in FIGS. 1-12, the mouthpiece (14) isexposed when the mouthpiece cover (2) is slid from the first position tothe second on the upper housing member (4 a) and the lower housingmember (4 b); the gear mechanism is triggered by the drive gear (12) andone dose of dry powder medicament is prepared for inhalation; thecounter gear (9) is indexed and the numeral seen through the displayaperture (4 c) on the lower housing member (4 b) is incremented. Afterthe inhalation is realized, the mouthpiece cover (2) is solely movedfrom the second position to the first position wherein the mouthpiece(14) is completely covered.

The medicament in dry powder form which is stored in blister cavities ismanufactured according to the prior art. According to the presentinvention, the particle sizes of the active agents comprised in the drypowder medicament are smaller than 20 μm, preferably smaller than 10 μm.

The inhaler pertaining to the present invention has been designed so asto deliver the dry powder medicament used in monotherapy or combinedtherapy. The term “monotherapy” refers to inhalation treatments in whichdry powder medicaments comprising a single active agent are used whereasthe term “combined therapy” refers to inhalation treatments in which drypowder medicaments comprising more than one active agents are use used.

The dry powder medicament delivered via the device pertaining to thepresent invention comprises at least one excipient in addition to theactive agent or agents. These excipients are generally chosen from agroup comprising monosaccharides (glucose, arabinose, etc.),disaccharides (lactose, saccharose, maltose, etc.), oligo- andpolysaccharides (dextran, etc.), polyalcohols (sorbite, mannite,xylite), salts (sodium chloride, calcium carbonate, etc.) orcombinations thereof. According to the present invention, the medicamentin dry powder form comprises lactose as the excipient. The medicament indry powder form comprises fine or coarse excipients particles preferablyhaving various particle size ranges in order to deliver the requiredamount to the lungs.

The active agent or the active agents comprised in the dry powdermedicament which is stored in blister packages used in the devicepertaining to the present invention can be selected from a groupcomprising cromolyns, anti-infectives, antihistamines, steroids,anti-inflammatories, bronchodilators, leukotirene inhibitors, PDE IVinhibitors, antitussives, diuretics, anticholinergics, hormones,xanthines and pharmaceutically acceptable combinations thereof.

The active agent comprised in the medicament in dry powder formdelivered via the inhaler pertaining to the present invention ispreferably selected from a group comprising tiotropium, oxitropium,flutropium, ipratropium, glicopironium, flunisolid, beclomethasone,budesonide, fluticasone, mometasone, ciclesonide, rofleponide,dexamethasone, montelukast, methylcyclopropane acetic acid, sodiumcromoglicat, nedocromil sodium, Npropylene, teophylline, roflumilast,ariflo (cilomilast), salmeterol, salbutamol, formoterol, terbutaline,carmoterol, indacaterol, cetirizine, levocetirizine, efletirizine,fexofenadine and their racemates, free base, enantiomers ordiastereomers and their pharmaceutically acceptable salts, solvatesand/or hydrates or a combination of said active agents.

The device pertaining to the present invention is used in theadministration of the medicament in dry powder form which is utilized inthe treatment of respiratory diseases, particularly in asthma, chronicobstructive pulmonary disorder (COPD) and allergic rhinitis.Accordingly, the respiratory diseases include, but not restricted to,allergic or non-allergic asthma at any phases, acute lung injury (ALI),acute respiratory distress syndrome (ARDS), exacerbation of airwayshyperactivity, bronchiectasis, chronic obstructive pulmonary includingemphysema and chronic bronchitis, airways or lung diseases (COPD, COADor COLD), pneumoconiosis, aluminosis, anthracosis, asbestosis,chalicosis, ptilosis, siderosis, silicosis, tabacosis and byssinosis.The device pertaining to the invention can be used in prophylactic orsymptomatic treatment. In addition, the medicament in dry powder formwhich is preferably used in the symptomatic treatment of allergic asthmaand COPD is administered to the patient via the device pertaining to thepresent invention.

What is claimed is:
 1. An inhaler suitable for delivery of a medicamentin dry powder form from a blister package (15) comprising a plurality ofblister pockets (15 a), each of which comprises the medicament and isspaced at equal intervals, the inhaler comprising: (a) a mouthpiece (14)enabling a patient to inhale the medicament, (b) a gear mechanismenabling the blister package (15) to be indexed and the medicament tobecome ready for inhalation, (c) a rotatable mouthpiece cover (2)covering the mouthpiece (14) and triggering the gear mechanism, (d) adrive gear (12) joined with the mouthpiece cover (2), and (e) a housing(10) situated between an upper housing member (4 a) and a lower housingmember (4 b) enclosing the blister package (15) and the gear mechanism,wherein an inside lock connection is provided between the mouthpiececover (2) and the drive gear by two ends (31 a, 31 b) of the drive gear(12) enabling the mouthpiece cover (2) to connect with the gearmechanism and engaging with recessed parts (30 a, 29 a) on the insideface of the mouthpiece cover through a male-female connection.
 2. Theinhaler according to claim 1, wherein the inhaler further comprises atleast one stopper (26) in the lower housing member (4 b).
 3. The inhaleraccording to claim 2, wherein the at least one stopper (26) engages withthe teeth of at least one gear and hinders its rotation.
 4. The inhaleraccording to claim 3, wherein the stopper (26) hinders the rotation ofan indexing ratchet wheel (3) in the gear mechanism.
 5. The inhaleraccording to claim 4, wherein the stopper (26) engages with the teeth ofthe indexing ratchet wheel (3) and hinders its rotation in order toprecisely position the blister package (15).
 6. The inhaler according toclaim 1, wherein the inhaler is an easy-grip, manual device suitable fordelivery of the medicament.
 7. The inhaler according to claim 1, whereinthe housing (10) comprises a beak (10) that peels the blister package(15) and a manifold (20) through which the medicament in the blisterpocket (15 a) passes during inhalation before reaching the mouthpiece(14).
 8. The inhaler according to claim 1, wherein the inhaler comprisesa path restricted by protrusions (23 a, 23 b; 24 a, 24 b) on the upper(4 a) and the lower (4 b) housing members.
 9. The inhaler according toclaim 8, wherein the mouthpiece cover (2) is rotatable by sliding alongthe restricted path.
 10. The inhaler according to claim 9, wherein themouthpiece cover (2) rotates by a fixed angle in the range of 30° to160° along a constant-distance path defined by the protrusion parts (23a, 23 b; 24 a, 24 b) in response to actuation of the inhaler.
 11. Theinhaler according to claim 1, wherein the mouthpiece cover (2) can be intwo positions, a first position wherein the mouthpiece cover (2) resideson protruding parts (23 a, 24 a) at one end of a rotational path,wherein the mouthpiece cover is completely covered and the inhaler is instandby mode; a second position, wherein the mouthpiece cover (2)resides on protruding parts (23 b, 24 b) at the other end of therotational path, wherein one dose of the medicament is ready forinhalation.
 12. The inhaler according to claim 1, wherein the inhalerfurther comprises a finger tab on the mouthpiece cover to move themouthpiece cover easily.
 13. The inhaler according to claim 1, whereinthe gear mechanism comprises: (a) the drive gear (12) which actuate theinhaler by transmitting the constant-angle movement of the mouthpiececover (2) to an indexing ratchet wheel (3); (b) an indexing wheel (8)which synchronizes with the indexing ratchet wheel (3) and enables theblister package (15) to be indexed in use; (c) a winding wheel gear (6)which moves a winding wheel (13) via a mechanism wheel (5) upon rotationof the indexing wheel (8); (d) a pinion gear (11) and (e) a base gear(7) that transmit the movement of the indexing wheel (8) to a counterwheel; (f) a counter gear (9) which displays the number of the unusedblister pockets (15 a) remaining in the inhaler.
 14. The inhaleraccording to claim 13, wherein components (a) through (f) directly orindirectly engage with each other.
 15. The inhaler according to claim13, wherein the indexing wheel (8) comprises 8 recesses (8 a) which arecomponents of the gear mechanism.
 16. The inhaler according to claim 15,wherein the angles between the recesses (8 a) are all equal and 45°. 17.The inhaler according to claim 15, wherein the shape of the recesses (8a) is the same shape as that of the blister pockets (15 a).
 18. Theinhaler according to claim 13, wherein the rotation of the indexingwheel (8) by an angle of 45° in response to each actuation of theinhaler is provided by an inside lock connection between the mouthpiececover (2) which rotationally moves at a fixed value in the range of 30°to 160° according to the shape of the inhaler.
 19. The inhaler accordingto claim 13, wherein the counter gear (9) comprises numerals equal tothe number of the blister pockets (15 a) to be inserted for use.
 20. Theinhaler according to claim 19, wherein the numerals are increments from1 to 60 equal to 60 blister pockets (15 a) each containing a single doseof the medicament.
 21. The inhaler according to claim 20, wherein theangles between the numerals on the counter gear (9) are of approximately5°.
 22. The inhaler according to claim 1, further comprising at leastone air inlet (22) on the upper housing member (4 a) to provide airflow.
 23. The inhaler according to claim 1, wherein the blister package(15) is a blister strip.
 24. The inhaler according to claim 23, whereinthe blister strip is peelable.
 25. The inhaler according to claim 23,wherein the blister package comprises a lid sheet (15 b) and a basesheet (15 c) comprising a plurality of layers.
 26. The inhaler accordingto claim 25, wherein the layers are selected from the group consistingof polymeric layers, aluminum foil, and fluoropoylmer film.
 27. Theinhaler according to claim 25, wherein at least one of the layerscomprises a desiccant agent selected from the group consisting of silicagel, zeolite, alumina, bauxite, anhydrous calcium sulfate, activatedcarbon, and clay.
 28. The inhaler according to claim 26, wherein thethickness of the aluminum foil is in the range of 5 to 80 μm.
 29. Theinhaler according to claim 28, wherein the thickness is in the range of15 to 65 μm.
 30. The inhaler according to claim 26, wherein thethickness of the polymeric layer is in the range of 5 to 100 μm.
 31. Theinhaler according to claim 30, wherein the thickness is in the range of15 to 60 μm.